Physical, Cognitive, Social, and Functional Health Correlates of Major Depressive Disorder Subtypes: A Systematic Review.

Background/objectives: Major Depressive Disorder (MDD) is a neuropsychiatric disorder affecting nearly 200 million people worldwide. While it has broad health effects, relatively little is known about how these vary across MDD 'subtypes', which reflect distinct symptom profiles. This systematic review examined the methods used to define several MDD subtypes and their associations with physical, cognitive, social, and functional health outcomes.

Methods: A systematic search of PubMed was conducted in accordance with PRISMA 2020 guidelines to identify peer-reviewed studies published in English between 2014 and 2025. The final search was conducted on 21 January 2025. Studies were included if they examined adults with MDD subtypes and reported health-related outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale. A narrative synthesis was conducted due to heterogeneity in the subtype definitions and outcome measures.

Results: Sixteen studies were included. Atypical and melancholic depression were most consistently associated with metabolic dysfunction, higher BMI, and a greater waist circumference. Melancholic depression was frequently associated with cognitive deficits, though results varied. Cognitive impairments were also observed in DSM-defined atypical depression, particularly in attention, vigilance, and social cognition. Anxious and melancholic depression may be associated with more severe social and functional impairment compared to other subtypes. However, the findings were limited by inconsistent definitions and outcome measures.

Conclusions: Some subtypes, particularly atypical, melancholic, and anxious depression, are differentially associated with specific patterns of impairment, though inconsistencies limit firm conclusions.

Registration: This review was retrospectively registered with the Open Science Framework (OSF): No specific funding was received.